Process for making (e)-7-(4-((5-((2-chlorobenzylidene)amino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Abstract

A process for making (E)-7-(4-((5-(2-chlorobenzylideneamino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid compound The process including: stirring a solution of 5-(2-chlorobenzylideneamino)-1,3,4-thiadiazole-2(3H)-thione and formaldehyde in ethanol to obtain a reaction mixture; adding ciprofloxacin HCl and triethylamine to the reaction mixture and stirring with reflux; cooling the reaction mixture at room temperature to obtain a solid; and obtaining the 7-(4-((5-(2-chlorobenzylideneamino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid compound. Its use as an anticancer and/or anti-inflammatory agent.

We claim: 
     
       1. A process for making (E)-7-(4-((5-((2-chlorobenzylidene)amino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid having the formula IV: 
       
         
           
           
               
               
           
         
         wherein the process comprises the following steps: 
         (1) stirring a solution of (E)-5-((2-chlorobenzylidene)amino)-1,3,4-thiadiazole-2(3H)-thione having the formula I: 
       
       
         
           
           
               
               
           
         
         
           and formaldehyde having the formula II: 
         
       
       
         
           
           
               
               
           
         
         
           in ethanol, to obtain a first reaction mixture; 
         
         (2) adding ciprofloxacin hydrochloride having the formula III: 
       
       
         
           
           
               
               
           
         
         
           and triethylamine to the first reaction mixture formed in step (1) above, to obtain a second reaction mixture; 
         
         (3) heating the second reaction mixture formed in step (2) above to reflux while stirring; 
         (4) cooling the reaction mixture formed in step (3) above to room temperature; and 
         (5) filtering the reaction mixture formed in step (4) above, to obtain a precipitate of (E)-7-(4-((5-((2-chlorobenzylidene)amino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid having the formula IV: 
       
       
         
           
           
               
               
           
         
       
     
     
       2. The process of  claim 1 , wherein, in step (1), the process further comprises stirring the first reaction mixture at room temperature for a period of at least 55 minutes prior to performing step (2). 
     
     
       3. The process of  claim 1 , wherein, in step (1), the process further comprises adding (E)-5-((2-chlorobenzylidene)amino)-1,3,4-thiadiazole-2(3H)-thione having the formula I and formaldehyde having the formula II in a molar ratio of 3:7. 
     
     
       4. The process of  claim 1 , wherein, in step (2), the process further comprises adding ciprofloxacin hydrochloride having the formula III and triethylamine to the first reaction mixture formed in step (1) in a molar ratio of 3:4. 
     
     
       5. The process of  claim 1 , wherein, in step (1) and step (2), the process further comprises adding (E)-5-((2-chlorobenzylidene)amino)-1,3,4-thiadiazole-2(3H)-thione having the formula I, formaldehyde having the formula II, ciprofloxacin hydrochloride having the formula III, and triethylamine in a molar ratio of 3:7:3:4. 
     
     
       6. The process of  claim 1 , wherein, in step (3), the process further comprises stirring the second reaction mixture for a period of at least 2 hours prior to performing step (4). 
     
     
       7. The process of  claim 1 , wherein, in step (5), the process further comprises:
 (a) washing the precipitate of (E)-7-(4-((5-((2-chlorobenzylidene)amino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid having the formula IV with water; and 
 (b) recrystallizing the precipitate of (E)-7-(4-((5-((2-chlorobenzylidene)amino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid having the formula IV from ethanol. 
 
     
     
       8. The process of  claim 7 , wherein the process further comprises obtaining (E)-7-(4-((5-((2-chlorobenzylidene)amino)-2-thioxo-1,3,4-thiadiazol-3(2H)-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid having the formula IV in a yield of 73%.